As our lab studies the role of sensory input on the formation and refinement of neural circuits within the olfactory system, much of our current focus is on understanding the basis of a robust form of cellular plasticity exhibited by a class of neurons in the olfactory bulb called external tufted cells which give rise to an intrabulbar map and ask how this plasticity is modulated by olfactory stimuli. [unreadable] [unreadable] We have previously described the dramatic anatomical basis of this plasticity which has no critical period (Marks et al., 2006), and are now extending these studies to explore the functional and molecular aspects of this plasticity as well. At an initial level we have carried out an extensive study to determine that loss of odorant induced activity disrupts the development organization and maintenance however, we have recently determined that re-introduction of normal odorant induced activity can precisely restore the anatomical organization of this map (manuscript in preparation). [unreadable] [unreadable] Using an electrophysiological approach we have also determined that intrabulbar connection have tremendous influence over sensory input as they can determine weather or not the output neurons of the bulb will be allowed to fire (manuscript in preparation). At a molecular level we are testing the function of several candidate proteins (i.e. BDNF, GDNF) thought to be playing an important role in olfactory development are also involved in regulating intrabulbar map plasticity perhaps helping to explain some the morphological changes that we observe. This aspect of our study is being conducted in part by a graduate student, Carolyn Marks, in association with the NIH-GPP program and in collaboration with Carlos Ibanez at the Karolinska Institute. In conjunction with this approach another student Joshua Bagley has established a slice imaging approach to determining the molecules that are involved in regulating the migration of central nervous system neurons to the olfactory bulb via the rostral migratory stream (RMS). It is our hypothesis that many of the molecules that organize the maps in the olfactory bulb are also involved in directing RMS neurons. [unreadable] [unreadable] In our previous studies, we have uncovered evidence that olfactory experience can shape primary sensory neuron projections to the bulb during early postnatal development (Kerr and Belluscio, 2006). We have also extending this study to older animals and revealed that by merely changing in the pattern of odorant-induced activity it is also possible to reorganize the glomerular map in adults (manuscript in preparation). Based upon these data a new student Emmette Hutchison has outlined a thesis project to determine the functional basis that underlies refinement of the glomerular map. Preliminary data that we have acquired using a synaptophlorin based imaging approach (uses pH sensitive GFP), Emmette has already revealed a number of interesting distinctions between the odorant response properties of glomeruli in P10 animals compared to adults. [unreadable] [unreadable] To understand experience dependent plasticity from the peripheral perspective we have are also exploring the regulation of odorant receptor gene expression in the sensory epithelium and in particular the role that odorant receptors play in axon guidance. We have determined that the odorant receptor which is located in the axon terminals of olfactory sensory neurons is interacting with two different classes of proteins each capable of producing a guidance phenotype when expression levels are altered (manuscript in preparation). Lastly, I have been invited to write a review for The Scientist on the topic of Neural Plasticity from an olfactory perspective which I am current working on with my post-doc Diana Cummings and will submit within the next several months (manuscript in preparation). [unreadable] [unreadable] On a broader planning level, we continue to collaborate with Alan Koretsky (NINDS) on questions of olfactory development and plasticity and Nick Ryba (NIDCR) on projects related to odorant receptor regulation and Ron McKay on the regeneration of olfactory bulb neurons. We also continue to have some difficulties in maintaining our animal colony, primarily related to space issues and lack of an animal care technician that is dedicated to our laboratory. Due to these difficulties we have been forced to sacrifice several of our lines that are either breeding poorly or not needed for the foreseeable future as we do not have the resources (time, space and man-power) to maintain them all. The unfortunate consequences of this approach are obvious in that if a line is deemed necessary at a later date we will face unavoidable delays in re-acquiring and establishing the line. Finally, on a more routine level, I continue to attend and participate in professional meetings and accept as many invited talks as possible.